CNS demyelinating disorder with mixed features of neuromyelitis optica and multiple sclerosis in HIV-1 infection. Case report and literature review.

An African-American male presented with bilateral visual impairment, gait difficulties, and bladder and bowel incontinence raising concerns for multiple sclerosis (MS) or neuromyelitis optica (NMO). He was identified to be HIV-1 infected with high viral load and low CD4+ counts. Magnetic resonance imaging (MRI) of the brain was abnormal, but atypical for MS. MRI of the cervical and thoracic spinal cord showed multiple areas of myelitis with a longitudinally extensive thoracic transverse myelitis that showed enhancement with gadolinium suggestive of NMO. Cerebrospinal fluid showed oligoclonal IgG bands but did not show reactivity to aquaporin 4. Patient underwent treatment for the acute exacerbation with intravenous corticosteroids and treatment of the HIV infection with highly active antiretroviral therapy (HAART). A year later, his viral load was <20 copies/ml and CD4+ counts were normal. Vision did not significantly improve, but his ambulation improved from a near total non-ambulatory state to ambulating without aids and resolution of the bladder and bowel incontinence. A demyelinating disorder of the central nervous system (CNS) like MS or NMO has been previously reported in the context of HIV infection. The remarkable improvement of symptoms has also been previously reported with HAART, and these observations have led to clinical trials of MS with HAART therapy in the absence of HIV infection. We reviewed the few cases of CNS demyelinating disorders with HIV infection reported in the literature and speculate on the mechanisms of pathogenesis.

Use of Calcitonin Gene-Related Peptide Monoclonal Antibodies for the Treatment of Migraines in Individuals With Multiple Sclerosis.

BACKGROUND: Migraines are a common comorbidity and source of disability in patients with chronic inflammatory diseases like multiple sclerosis (MS). Recently, therapeutic agents for episodic and chronic migraine known as calcitonin gene-related peptide (CGRP) inhibitors have shown to effectively control migraine attacks and improve quality of life in the general population. This study explored the use of these novel agents in individuals with comorbid MS. METHODS: This was a retrospective, population-based cohort study at the University of South Florida's neurology clinic; it evaluated individuals with both MS and migraine. RESULTS: A total of 27 individuals with MS and chronic or episodic migraine who received treatment with a CGRP monoclonal antibody were identified. Of these, 63% reported a reduction in their migraine frequency of greater than 75%. Concurrent use of a disease-modifying therapy (DMT) for MS occurred in 82% of patients, and in 37% of these, the DMT used was also a monoclonal antibody. Adverse effects from CGRP monoclonal antibodies were mild and occurred in only 11% of patients, and no patient experienced worsening of their MS symptoms during cotreatment over the duration of the study. CONCLUSIONS: Our study showed a significant reduction in migraine frequency and a favorable adverse event profile for individuals with comorbid MS who took CGRP monoclonal antibodies and experienced no worsening of MS symptoms. In individuals with MS, CGRP monoclonal antibodies seem to be a safe and effective therapy for episodic or chronic migraine.

Multiple Sclerosis and MyChart Messaging: A Retrospective Chart Review Evaluating Its Use.

BACKGROUND: Understanding patterns of MyChart (Epic Systems Corporation) messaging has the potential to alter clinical practice. However, because most research evaluating its use has been conducted in limited contexts, utilization patterns in patients with multiple sclerosis (MS) remain unclear. We characterized factors associated with high rates of MyChart messaging for patients with MS at an academic outpatient clinic. METHODS: We performed a retrospective cross-sectional analysis of 439 patients in our center's database. Inclusion criteria were 1 or more clinic visits and MS diagnosis. We extracted demographic data, disease-specific characteristics, and MyChart messaging information. RESULTS: Of the patients in the database, 324 (74%) were MyChart users. MyChart users were more often younger (mean ± SD age, 50.1 ± 12.6 vs 55.0 ± 13.7 years; P < .001), had shorter mean ± SD duration since diagnosis (11.9 ± 8.3 vs 15.8 ± 10.8 years; P = .0013), had lower mean ± SD Patient-Determined Disease Steps scale scores (2.8 ± 2.3 vs 3.5 ± 2.5; P = .0107), and were more likely to be using high-efficacy disease-modifying therapies (χ2 1,323 = 6.7; P = .009). Messaging rates correlated positively with total number of unique medications (R = 0.17; P = .003) and negatively with age (R = -0.11; P = .018). CONCLUSIONS: Although previous research has implicated arm-hand disability and impaired vision as barriers to patient portal use, these findings suggest the relationship between MS-specific disease burden and MyChart utilization is also a function of underlying medical complexity beyond physical disability. These data may serve as groundwork for investigations in other disease-specific settings and for quality improvement research to mitigate these high rates in at-risk patients to optimize provider time investment, clinic productivity, and patient safety and minimize health care provider burnout.

Assessing Barriers to Adherence with the Use of Dimethyl Fumarate in Multiple Sclerosis.

BACKGROUND: Multiple sclerosis (MS) is a chronic, inflammatory, central nervous system demyelinating disease that requires long-term use of disease-modifying therapies (DMT). Patient adherence to DMT is key in reducing the inflammation that leads to relapses and neurodegeneration. Dimethyl fumarate (DMF) poses unique challenges to adherence including being the only twice-daily dosing DMT. Previous research suggests there are direct roles that providers play on improving their patients' adherence rates, such as focusing on the patient-provider relationship, helping put the patient at ease so that they feel understood and respected. Also, route of administration affects adherence in other chronic healthcare conditions. However, the issue of adherence to DMT in MS is more complex than just route of administration, with adverse effects being the main predictor of adherence. OBJECTIVES: (1) To define various patient specific factors (e.g. fatigue and mood disorders) that affect adherence with DMF and (2) to understand how patients' perceptions of treatment satisfaction (such as effectiveness, convenience, side effects and global satisfaction) and DMFs impact on quality of life (such as social support, activities of daily living, coping) influence adherence. METHODS: Our study was a prospective, observational measurement of adherence to treatment with DMF in MS patients over 52 weeks. Twenty-five out of thirty-five patients enrolled completed the study. Adverse event (AE) data was reviewed on all participants. RESULTS: Adherence rates correlated with patient's perceived effectiveness (0.25, p < 0.023) and the level of bothersome symptoms the patient experienced (0.45, p < 0.0001). The majority of new AE onset was reported within 12 weeks of DMF initiation. This is consistent with previously published data with DMF use. CONCLUSION: Adherence rates are an important factor to be considered when starting patients on DMT. DMF creates its own barriers to adherence with our study highlighting some, including twice-daily dosing and AEs experienced following treatment initiation. Healthcare providers should be aware of these barriers prior to treatment initiation and counsel patients appropriately.

Tolerability and efficacy of colestipol hydrochloride for accelerated elimination of teriflunomide.

BACKGROUND: Teriflunomide is an oral disease modifying therapy approved for the treatment of relapsing forms of multiple sclerosis. Teriflunomide' s pharmacokinetics (PK) contribute to its slow elimination, on average taking 6-8 months, though it can take up to 2 years in some instances. This slow elimination can become problematic in certain clinical situations - such as during pregnancy, when teriflunomide has potential teratogenic effects. In such scenarios, an accelerated elimination procedure (AEP) is recommended. Currently, AEPs with oral cholestyramine or activated charcoal are available but are restricted by adverse effects, limited administration routes, and dosing frequencies. METHODS: A single-center, PK interaction study was performed in a total of 14 healthy volunteers, to investigate colestipol hydrochloride (HCl) as an alternative to cholestyramine for the elimination of teriflunomide. Participants received teriflunomide for 14 days, followed by an AEP with colestipol HCl for 15 days. RESULTS AND CONCLUSIONS: The administration of colestipol HCl for 15 days was sufficient to reduce plasma teriflunomide concentrations by greater than 96%. Although colestipol HCl did not completely eliminate teriflunomide with the same effectiveness as cholestyramine, it may offer an alternative method for accelerated elimination of teriflunomide with potentially improved tolerability and more favorable dosing and administration options.

Neuroleptic Malignant Syndrome Associated with Refractory Acute Disseminated Encephalomyelitis.

We present the case of a young man who was transferred to our hospital with worsening acute disseminated encephalomyelitis (ADEM) despite treatment with intravenous methylprednisolone, intravenous immunoglobulin and plasma exchange. He developed neuroleptic malignant syndrome (NMS) without the use of dopamine-modulating drugs. His progressive clinical improvement started after treatment with intravenous cyclophosphamide and methylprednisolone. In our patient, acute demyelination with severe bilateral inflammation of the basal ganglia could have caused a state of central dopamine depletion, creating proper conditions for the development of NMS. Significant clinical improvement of our case after treatment with intravenous cyclophosphamide and steroids provides further evidence for a possible role of the inflammatory lesions in the pathogenesis of NMS in association with ADEM.

The effects of isolated brainstem lesions on human REM sleep.

BACKGROUND: Clinical and electrophysiologic data support the role of multiple brainstem structures responsible for sleep architecture. To determine if patients with isolated brainstem lesions have detectable abnormalities of sleep architecture with polysomnography (PSG). METHOD: The objective of this study is to determine if patients with isolated brainstem lesions defined by magnetic resonance imaging (MRI), and without sleep complaints, underwent PSG. The data was compared to age-matched controls. Eight patients met inclusion criteria. Of the eight locations, one was midbrain, two were pontomesencephalic, four were pontine and one was pontomedullary. RESULTS: Four of the eight patients had a decreased percentage of Rapid Eye Movement (REM) sleep. The abnormal studies occurred in patients with a right paramedian pontine infarct, a left pontomedullary cavernous hemangioma (CH), a left pontine CH, and a right pontomesencephalic CH. REM sleep, as a percentage of total bed time, was 8.7, 12.3, 14.8, and 16.7%, respectively. CONCLUSION: These findings concur with non-human data that depict pontine structures as the major generators of REM sleep.

Tratamiento farmacológico de dolor neuropático de tipo central en pacientes con esclerosis múltiple / Systematic review of the literature: pharmacologic therapy in central neuropathic pain for multiple sclerosis patients

Conclusiones: La disminución significativa del dolor neuropático de tipo central en pacientes que padecen esclerosis múltiple se presentó con la molécula dronabinol, los efectos secundarios fueron leves, siendo los más comunes: vértigo, somnolencia, boca seca y alteraciones en el equilibrio. La evidencia de los estudios de tratamiento de dolor neuropático en esclerosis múltiple con cannabinoides no son conclusivos y es necesario realizar ensayos clínicos con la molécula de dronabinol vs otras farmacoterapias y placebo para así proveer mayor información de la dosis terapéutica eficaz y segura para el tratamiento. Se requieren de más estudios clínicos basados en la evidencia respecto al tratamiento del dolor neuropático de tipo central en esclerosis múltiple dado que es una patología cada día de mayor incidencia poblacional y es necesario realizar estudios donde se presenten resultados específicos que comparen y muestren los medicamentos con mayor efectividad y menos efectos secundarios que eviten el abandono del tratamiento por parte de los pacientes y que garanticen una mejor calidad de vida.

Conclusions: The significant reduction of neuropathic pain in patients with central type with multiple sclerosis presented with dronabinol the molecule, the side effects were mild, the most common: dizziness, drowsiness, dry mouth and changes in the balance. Evidence from studies of the treatment of neuropathic pain in multiple sclerosis cannabinoids are not conclusive and need to conduct clinical trials with the molecule of dronabinol and other drug vs. placebo in order to provide more information on the safe and effective therapeutic dose for treatment. Further studies are needed evidence-based clinical trials regarding the treatment of central neuropathic pain such as multiple sclerosis is a disease every day with the highest incidence and population studies are needed where specific results are presented comparing drugs and show greater effectiveness and fewer side effects that prevent the abandonment of treatment by patients and ensure a better quality of life.

Efectividad y efectos secundarios del tratamiento con canabinoides en dolor neuropático de tipo central en pacientes con esclerosis múltiple / Eficácia e efeitos secundários do tratamento com canabinóides em dor neuropática tipo central en pacientes con esclerose múltipla / Effectivity and side effects of central neuropathic pain treatment with cannabinoids in patients with multiple sclerosis

La Esclerosis Múltiple (EM) es una enfermedad neurodesmielinizante de origen inmunológico que afecta a personas entre los 16 a los 35 años de edad y en la cual del 36% al 82% de los pacientes manifiestan dolor como síntoma común. La EM tiene una prevalencia mundial de 4,41 por cada 100.000 habitantes, afectando alrededor de 2,5 millones de personas en todo el mundo y cerca de 400.000 en Estados Unidos; en Colombia es de 4,3 por cada 100.000 habitantes, presentándose la mayoría de los casos en Risaralda seguido por Bogotá. Los síndromes de dolor neuropático de tipo central se presentan por lesión o disfunción del sistema nervioso central, causando discapacidad y deterioro de la calidad de vida de los pacientes. En este artículo se hace una revisión sobre la efectividad analgésica y efectos secundarios de los canabinoides en el tratamiento de dolor neuropático de tipo central en pacientes con EM. Se realizó una estrategia de búsqueda identificando ensayos clínicos aleatorizados sobre tratamientos de dolor neuropático de tipo central en EM con canabinoides y se seleccionaron seis estudios que compararon canabinoides vs placebo. Basados en los artículos revisados se puede concluir, que hay una disminución significativa del dolor neuropático de tipo central en pacientes que padecen EM con la administración de canabinoides y los efectos secundarios son leves, siendo los más frecuentes vértigo, xerostomía, somnolencia y alteraciones en el equilibrio los cuales no alteran la calidad de vida del paciente...

Multiple Sclerosis (MS) is an immunological neuro-demyelinating disease that affects population between 16 to 35 years. Pain is the most common symptom with 36% to 82% of patients reporting pain. MS has a worldwide prevalence of 4.41 per 100,000 people, affecting about 2.5 million people around the world and 400,000 in the United States; in Colombia 4.3 per 100,000 inhabitants suffer from this disease where most of the cases have been reported in the region of Risaralda and the capital city Bogotá. Central neuropathic pain syndrome is due to injury and dysfunction of the central nervous system, causing disability and impairing quality of life of patients. In this article, a review of the analgesic effectiveness and side effects of cannabinoids in the treatment of central neuropathic pain in patients with MS is conducted. A search strategy was performed to identify randomized clinical trials on the treatment of central neuropathic pain in MS with cannabinoids; six selected studies comparing cannabinoids versus placebo were selected and after analyzing them, it was found a significant decrease in pain with dronabinol (cannabinoid) treatment and low side effects. The most common side effects were drowsiness, dry mouth, dizziness and impaired balance, which did not compromise the quality of life of patients. Based on the review of articles it is concluded that there is a significant reduction in central neuropathic pain in patients with MS in therapy with cannabinoids and that side effects of treatment are very low...

Esclerose Múltipla (EM) éumadoençaneurodesmielinizante de origemimune que afetapessoas entre 16 e 35 anos, onde 36% a 82% dos pacientes relatamdor como umsintomacomum. MS temumaprevalência mundial de 4,41 por 100.000 pessoas, afetando cerca de 2,5 milhões de pessoas no mundo e cerca de 400.000 nos Estados Unidos; naColômbia é de 4,3 por 100.000 habitantes, apresentando-se a maioria dos casos em Risaralda seguida por Bogotá. Síndromes de dorneuropática do tipo central sãoapresentadas por umalesãooudisfunção do sistema nervoso central, causando incapacidade e redução da qualidade de vida dos pacientes. Nestetrabalho, umaanálise da eficácia analgésica e efeitoscolaterais dos canabinóides no tratamento do tipo de dorneuropática central em pacientes com EM. Realizamos umaestratégia de pesquisa para identificar estudos clínicos randomizados sobre o tratamento da dorneuropáticaem MS tipo central comcanabinóides, furam seis estudosselecionados comparando canabinóides versus placebo. Com base nos artigosconcluem que háumaredução significativa da dorneuropática da tipo central em pacientes com EM com a administração de canabinóides e os efeitoscolateraissão leves, os maiscomunssão tontura, sonolência, xerostomia e distúrbios do equilíbrio que nãoalterou a qualidade de vida dos pacientes...